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Photodynamic therapy (PDT) has been widely used in dermatology to treat different skin diseases. Here, we aim to compare the efficacy of single versus multiple fraction light illumination PDT for high grade lesions of cutaneous leishmaniasis (CL). In particular, 60 patients (104 CL lesions) were randomly divided into two groups; 30 patients (46 CL lesions) in group I were treated with methylaminolevulinate (MAL)-based PDT in three sessions, with a light dose of 90 J/cm 2 delivered in a single fraction in each session. The 30 patients (58 CL lesions) in group II received the same treatment, except the light dose in each session was delivered in three fractions. Patient assessment at nine months follow-up revealed complete response at 35 (76 %) for group I, compared to 53 (91.4 %) for group II. Moreover, partial response was observed in 11 (24 %) CL lesions for group I, as compared with 5 (8.6 %) CL lesions in group II. Pain and burning sensation in patients from group II was markedly less than patient from group I. In conclusion, fractionated illumination improves the treatment efficacy of PDT for high grade CL lesions., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)